Format

Send to

Choose Destination
Cell Rep. 2018 Dec 26;25(13):3661-3673.e3. doi: 10.1016/j.celrep.2018.11.098.

Culling Less Fit Neurons Protects against Amyloid-β-Induced Brain Damage and Cognitive and Motor Decline.

Author information

1
Cell Fitness Lab, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisbon, Portugal; Institute for Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland.
2
Stem Cells and Regeneration Lab, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisbon, Portugal.
3
Institute for Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland; Department of Biochemistry, University of Geneva, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland.
4
Institute for Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland.
5
Institute for Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland; Stem Cells and Regeneration Lab, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisbon, Portugal. Electronic address: christa.rhiner@research.fchampalimaud.org.
6
Cell Fitness Lab, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisbon, Portugal; Institute for Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland. Electronic address: eduardo.moreno@research.fchampalimaud.org.

Abstract

Alzheimer's disease (AD) is the most common form of dementia, impairing cognitive and motor functions. One of the pathological hallmarks of AD is neuronal loss, which is not reflected in mouse models of AD. Therefore, the role of neuronal death is still uncertain. Here, we used a Drosophila AD model expressing a secreted form of human amyloid-β42 peptide and showed that it recapitulates key aspects of AD pathology, including neuronal death and impaired long-term memory. We found that neuronal apoptosis is mediated by cell fitness-driven neuronal culling, which selectively eliminates impaired neurons from brain circuits. We demonstrated that removal of less fit neurons delays β-amyloid-induced brain damage and protects against cognitive and motor decline, suggesting that contrary to common knowledge, neuronal death may have a beneficial effect in AD.

KEYWORDS:

Alzheimer’s; Drosophila; apoptosis; azot; cell competition; cell fitness; neurodegeneration; neuronal selection; β-amyloid

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center